Muscarinic receptor antagonists, such as tolterodine, are known for the treatment of overactive bladder. However, an adverse side effect of these treatments is severe dry mouth. This side effect causes significant patient discomfort and reduces compliance greatly. Previous work has shown that the combination of tolterodine or oxybutynin with pilocarpine, a muscarinic receptor agonist that increases saliva formation, can significantly reduce the incidents of dry mouth while not affecting the efficacy of the muscarinic receptor antagonist. See, for example, U.S. Pat. Nos. 7,666,894, 7,678,821, and 7,781,472, and U.S. Application Publication Nos. 2009/0275629 and 2010/0152263, all of which are incorporated herein by reference in their entirety.
As discussed in the aforementioned publications, one cannot simply take a muscarinic antagonist and pilocarpine or cevimeline and expect to obtain the desired clinical efficacy. The timing of the administration of the muscarinic agonist vis-à-vis the administration of the muscarinic antagonist has to be adjusted properly so that the maximum increase in saliva formation due to the administration of the muscarinic agonist is reached at the same time as the maximum dry mouth experienced due to the administration of the muscarinic antagonist. Taking two tablets at two different times, where the time difference between the two administrations has to be exact, is inconvenient, cumbersome, and reduces patient compliance. Therefore, a single pharmaceutical formulation is needed where the desired time delay and release profile are incorporated.